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BALANCE AND
DISORDERS
12/8/21 By
Dr Madanika P
Ions Na+ K+
Cell
• Definition: Any particle Ca++
PO4---
which carries charge Cl- ECF
• Types:
●
Negatively charged . Move towards
Anions ●
anode
Eg: Cl- , HCO3-,PO43-, OH -
●
Positively charged. Move towards
Cations ●
Cathode
Eg: K+,Na+ ,Ca2+ ,H+,
12/8/21
Why charges on molecules are important?
12/8/21
H+ ion -it must be
maintained in narrow
range in order to be
compatible with living
systems
Free H+ ion –40nmol/L
Being small ion highly
reactive
Small fluctuation can
affect normal functions
Buffers regulate the
H+ ion concentration
4
Importance of Hydrogen Ion
• Creates a gradient across
membrane
• Maintenance of PH of body
fluids
• Gradient is important
To stimulate oxidative
phosphorylation
Ionisation of weak acids and
bases and facilitates their
physiological function
Affects surface charge of Proteins
12/8/21
Arrhenius theory
1887--- Ionic theory
1. Electrolyte splits into charged particles(ions)
in solution .
2. Ions carry electric current
3. Positive charges = Negative charges. Solution
is neutral.
4. Degree of ionization increases with dilution
in weak electrolytes.
5. Chemical changes occur due to reaction
between charges and not molecules.
12/8/21
Definition
• Acid is any substance which
dissociated in water to produce H+ ion
• Base is any substance which
dissociated in water to produce OH- ion
12/8/21
Bronsted and Lowry concept
9
ACIDS
• Acids can be defined as a proton (H+) donor
• Hydrogen containing substances which
dissociate in solution to release H+
Click Here
10
ACIDS
• Acids can be defined as a proton (H+) donor
• Hydrogen containing substances which
dissociate in solution to release H+
H+
OH
H+ -
OH-
H+
O -
H-
OH
H+
11
ACIDS
• Physiologically important acids include:
– Carbonic acid (H2CO3)
– Phosphoric acid (H3PO4)
– Pyruvic acid (C3H4O3)
– Lactic acid (C3H6O3)
• These acids are dissolved in body fluids
Phosphoric acid
Lactic acid
Pyruvic acid
12
BASES
13
BASES
• Bases can be defined as:
– A proton (H+) acceptor
– Molecules capable of accepting a hydrogen
ion (OH-)
Click Here
14
BASES
• Physiologically important bases include:
– Bicarbonate (HCO3- )
– Biphosphate (HPO4-2 )
Biphosphate
15
Conjugate acids and bases
12/8/21
Lewis acid Base Concept-1923
• Base: Any substance which donates a pair of
electrons
• Acid: Any substance which accepts a pair of
electrons
12/8/21
Sources of Acids & Bases in body
ACIDS BASES
• Gastric Juice-HCl Protein metabolism
• Cellular respiration- CO2 (deamination) -Ammonia
• Blood, Pancreatic juice-
Metabolic end products -
Organic acids Bicarbonate
• Dietary sources- Citrus
Blood- Carbonic acid
• Amino acid/Protein fruits - Bicarbonate,
metabolism- Sulphuric, Phosphates etc
Phosphoric acid
12/8/21
Acids Bases
Fixed acids Volatile acids Ammonia
lactate, pyruvate, acetoacetate, uric acid carbon dioxide Bicarbonate
12/8/21
pH ---Potential Hydrogen
Definition: Negative logarithm of
hydrogen ion concentration
• PH= - Log [H+]
• Expresses hydrogen ion concentration in solutions
• Water ionizes to a limited extent to form equal amounts of H+ ions and
OH- ions.
• It is Amphoteric
H 2O H+ + OH-
• H+ ion is an acid
• Hydroxonium ion is an acid
• OH- ion is a base
Venous Arterial
22 Blood Blood
pH SCALE
23
CHANGES IN CELL EXCITABILITY
• pH decrease (more acidic) depresses the
central nervous system
– Can lead to loss of consciousness
• pH increase (more basic) can cause over-
excitability
– Tingling sensations, nervousness,
muscle twitches
24
INFLUENCES ON ENZYME ACTIVITY
• pH increase or decrease can alter the shape of
the enzyme rendering it non-functional
• Changes in enzyme structure can result in
accelerated or depressed metabolic actions
within the cell
25
Dissociation Constant (KA)
• Definition: It is a constant ratio between
dissociated and un dissociated particles
12/8/21
Henderson Hesselbach’s equation
For an acid,
• PH = Pka + Log [base]/[acid] or
• PH = Pka + Log [Salt]/[acid]
• PH =Pka when Concentration of acid =
concentration of base (half dissociated).
12/8/21
Types
• Strong Acids and Bases: Those which
dissociate completely.
Eg: HCl and NaOH
12/8/21
ACIDOSIS ALKALOSIS
A relative increase in A relative increase in
hydrogen ions results in bicarbonate results in
acidosis alkalosis
H+ OH - H +
OH -
29
Regulation of Acid Base Balance in Body
H +
HCO3 -
12/8/21
ACID-BASE BALANCE
Derangements of
hydrogen and
bicarbonate
concentrations in
body fluids are
common in disease
processes
31
Three systems regulating Acid
base balance
Buffer
system
Respiratory
Renal system
12/8/21 32
system
Buffers
• Definition : These are solutions
or substances which resist change
in PH which is expected on addition
of acid or base.
12/8/21
Action of buffer
acid base
Buffer Buffer
pH 7.0 pH 7.0
pH 6.8 pH7.2
12/8/21
Types of Buffers
58% - 52% tissues 42% - 40% -Bicarbonate,
6% RBCs 1% Phosphate,1% Protein
12/8/21
Bicarbonate Buffer
• Most important buffer
• Main buffer in ECF (40%)—65% in plasma, but also
ICF ( RBCs)
• It converts strong non volatile to volatile acids
• Works in association with renal and respiratory
system
• Transporter of Carbon dioxide in plasma
12/8/21
BICARBONATE BUFFER SYSTEM
Predominates in extracellular fluid (ECF)
41
BICARBONATE BUFFER SYSTEM
This system is most important because the
concentration of both components can be
regulated:
– Carbonic acid by the respiratory system
– Bicarbonate by the renal system
42
BICARBONATE BUFFER SYSTEM
CO2 + H2O H2CO3 H+ + HCO3-
Hydrogen ions generated by metabolism or by
ingestion react with bicarbonate base to form more
carbonic acid
H2CO3 HCO3-
43
Representation of Bicarbonate buffer
• PH= Pka+ log [ HCO3-] / [H2CO3]
PH =7.4, [HCO3-]= 24mEq/L,
[H2CO3]=1.2mEq/L
• Hence on substituting ,
PKa= 6.1
• PH>Pka –Not an ideal buffer but
high concentration in plasma makes
it the best buffer
• Replenished continuously
• Base : Acid = 20:1 ( Alkali reserve)
12/8/21
45
Phosphate buffer
• Important intracellular buffer
• Urinary buffer ( Acidification of
urine)
• Acts best at physiological pH(pKa
= 6.8)
• Wide range buffer. Most effective
• Ratio of 4:1( Alkali reserve)
• Low concentration (1mmol/L).not
a major buffer
• Regulated by the renal system
12/8/21
PHOSPHATE BUFFER SYSTEM
Na2HPO4 + H+ NaH2PO4 +Na+
Most important in the intracellular system
Alternately switches Na+ with H+
Disodium hydrogen
phosphate
H + + Na2HPO4
– Too low of a
concentration in
ECF to have much HPO4 -2
importance as an
ECF buffer system
48
PROTEIN BUFFER SYSTEM
– Behaves as a buffer in both plasma and cells
– Hemoglobin is by far the most important protein
buffer in RBCs
– Plasma Proteins (Albumin) in ECF
Ionisable groups
Most abundant -Acidic & Basic
in body(75%) Amphoteric nature
Act instantly
with
millisec Na Pr/HPr
KPr/HPr
Carbamino compound 49
Carrier of CO2
Pr - added H+ + Pr -
H+ H+ H+ H+ H+ OH- H+ OH-
OH- H +
H+ OH-
OH- - - -+ - - - -- H+
- + ++
++ + -
- - + + + OH-
- -+ +
+ + - H+
H-+
OH -- +
-
- + - H+
- + +++
- + + - OH-
H+
- + + - H+
OH-
+
- - - - - - - -
OH- OH- H+
H + H
+
H+ HOH
+ -
H+ H +
51
Hemoglobin buffer
Hemoglobin is better buffer than plasma proteins
12/8/21
As hemoglobin releases O2 it gains a great affinity for H+
ISOHYDRIC TRANSPORT OF CARBON DIOXIDE
Hb 54
O O
• Venous blood is only slightly more acidic than
arterial blood because of the tremendous
buffering capacity of Hb
• Even in spite of the large volume of H+
generating CO2 carried in venous blood
55
Cellular buffers
• Cellular pH = 6.8-7.2 H+
important role K+
cell
• trancellular shift is seen
• Mainly in skeletal tissue & bone
12/8/21
ELECTROLYTE SHIFTS
K+
57 57
INFLUENCES ON K LEVELS +
K+ Na+
H+
58
1) Buffer Systems
2) Respiratory Responses
3) Renal Responses
4) Intracellular Shifts of Ions
59
Respiratory Regulation
• Second line of defence
• Acts in minutes
• Acts by,
1. Exchange of gases(regulates pCO2)
2. Regulates Carbonic acid levels (with
Bicarbonate buffer)
3. Chemo receptors are pH sensitive
regulating respiratory rate
12/8/21
ISOHYDRIC TRANSPORT OF CARBON DIOXIDE
12/8/21
RESPIRATORY CENTER
Stimulation and limitation of
respiratory rates are controlled by
the respiratory center
Pons
Respiratory centers
Medulla oblongata
Control is accomplished by
responding to CO2 and H+
62
concentrations in the blood
CHEMOSENSITIVE AREAS
• Chemo sensitive areas of the respiratory center
are able to detect blood concentration levels of
CO2 and H+
• Increases in CO2 and H+ stimulate the respiratory
center
– The effect is to raise
respiration rates
– But the effect
diminishes in
1 - 2 minutes
CO
CO
CO
2
22
Click to increase CO2 CO
CO
CO2
2 2CO 63
CO
CO22
CHEMORECEPTORS
• Chemo receptors are also present in the carotid
and aortic arteries which respond to changes in
partial pressures of O2 and CO2 or pH
• Increased levels of
CO2 (low pH) or
decreased levels of
O2 stimulate
respiration rates
to increase
64
CHEMORECEPTORS
Overall compensatory response is:
– Hyperventilation in response to increased
CO2 or H+ (low pH)
– Hypoventilation in response to decreased
CO2 or H+ (high pH)
65
RESPIRATORY CONTROL OF pH
cell production of CO2 increases
H2CO3 H+ + HCO3-
H+ acidosis; pH drops
67
RENAL RESPONSE
• The kidney compensates for Acid - Base imbalance
within 24 hours and is responsible for long term control
• The kidney responds in 4 ways:
1. Excretion of H+ Ion
2. Reabsorption of HCO3-
3. Excretion of Titratable acid
4. Excretion of NH4+ ions
– In Acidosis
• Retains bicarbonate ions and eliminates hydrogen
ions
– In Alkalosis
• Eliminates bicarbonate ions and retains hydrogen
ions 68
ACIDIFICATION OF URINE BY EXCRETION OF HYDROGEN
Capillary Distal Tubule Cells Notice the
H+ - Na+ exchange t
maintain electrica
neutrality
Dissociation of
carbonic acid
Na+ +
H23CO
HCO -
+3 H+
NaHCO3
NaHCO3
H2O+CO2
Click MouseHto See
Animation Again Tubular 69
12/8/21
ACIDIFICATION OF URINE BY EXCRETION OF AMMONIA
Distal Tubule Cells
Capillary
Glutamine- NH2
Glutamine
NH
NH3 3 H++
WHAT
HAPPENS
NEXT?
Tubular urine to
be excreted
71
ACIDIFICATION OF URINE BY EXCRETION OF AMMONIA
Distal Tubule Cells
Notice the
Capillary
H+ - Na+
NH3 exchange to
maintain
electrical
Dissociation of neutrality
carbonic acid
NaNaCl
+
+ Cl-
HCO -
H32CO+3 H+
NaHCO3
NaHCO3
NH3Cl-
NH4Cl
Click
Click Mouse
Mouse to See
to Start Tubular Urine 72
RESPIRATORY & EXCRETORY
RESPONSE
CO2 + H2O H2CO3 H+ + HCO3-
Hyperventilation removes
H+ ion concentrations Kidneys eliminate or retain
H+ or bicarbonate ions
Hypoventilation increases
73
H+ ion concentrations
1) Buffer Systems
2) Respiratory Responses
3) Renal Responses
4) Intracellular Shifts of Ions
74
HYPERKALEMIA
• Hyperkalemia is generally associated with
acidosis
– Accompanied by a shift of H+ ions into cells
and K+ ions out of the cell to maintain
electrical neutrality
H +
K +
75
HYPOKALEMIA
• Hypokalemia is generally associated with
reciprocal exchanges of H+ and K+ in the
opposite direction
– Associated with alkalosis
• Hypokalemia is a depressed serum K+
H +
K +
76
Disorders Of Acid Base
Balance
D
Abnormalities in the acid base balance of the body associated
12/8/21
with change in Plasma pH
Abnormal functioning of
Respiratory or Renal
system
Accumulation or loss of
acids or bases in the body
Exogenous administration
or endogenous production
Compensatory
mechanisms bring the pH
to near normal
H +
HCO 3
-
78
ACIDOSIS ALKALOSIS
A relative increase in A relative increase in
hydrogen ions results in bicarbonate results in
acidosis alkalosis pH > 7.45
pH < 7.35
H + OH - H +
OH -
79
Classification
• Simple ABD
Based on the Source and direction in which pH is altered
– Respiratory Acidosis
Respiratory system
– Respiratory Alkalosis affected
– Metabolic Acidosis
Renal system
– Metabolic Alkalosis affected
12/8/21
ACIDOSIS
Causes
1. Increase in Acid:
– Increase in H2CO3 (CO2)
– Increase in Non carbonic acids
2. Decrease in Base
– A decrease in HCO3-
Both lead to a decrease in the ratio of 20:1
H2CO3 HCO3 -
81
ACIDOSIS
decreased failure of metabolic production absorption of prolonged
removal of kidneys to acid of keto acids metabolic acids diarrhea
CO2 from excrete from GI tract
lungs acids
Deep
vomiting
from
Respiratory Metabolic GI tract
Increase in
acidosis plasma H+ acidosis
concentration Kidney
disease
(uremia)
Depression of
nervous system 82
ALKALOSIS
Causes
1. Decrease in Acid:
– Decrease in H2CO3 (CO2)
– Decrease in Non carbonic acids
2. Increase in Base
– Increase in HCO3-
Both lead to a Increase in the ratio of 20:1
H2CO3 HCO3 -
83
ALKALOSIS
anxiety overdose high prolonged ingestion of excess
of certain altitudes vomiting excessive aldosterone
drugs alkaline drugs
respiratory metabolic
alkalosis alkalosis
decrease
in plasma H+
concentration
overexcitability
of nervous
system 84
Compensation
Occurs in same direction as the primary
variable by changing the counter variable
Buffers are the first line of defence
Respiratory system takes action in minutes
Renal system brings back the pH to normal
12/8/21
12/8/21
ACIDOSIS
H+
1) Respiratory Acidosis
2) Metabolic Acidosis H+
H+ H+
H + H+
H + H H +
+ + H +
H H +
H + H + H +
H +
H + H H
+ + H +
H + H +
H + H +
H+ H + H +
H+ H+ H+ H+ 87
ALKALOSIS
• 1) Respiratory alkalosis H+
• 2) Metabolic alkalosis H+
H+ H+
H+
H+ H+
H+ H+ H+
H+ H+
H + H+
H+ H+ 88
Anion Gap
• The major cation is
Na+
– Minor cations are
K+, Ca2+ , Mg2+
• The major anions are
HC03- and Cl-
(Routinely measured.)
Uses:
To classify Metabolic Acidosis
Treatment of these disorders
Anion Gap
METABOLIC ACIDOSIS
Definition: Increase in plasma pH associated
with primary increase in acid or deficiency
of Bicarbonate
12/8/21
METABOLIC ACIDOSIS
• Occurs when there is a decrease in the normal
20:1 ratio
Decrease in blood pH and bicarbonate level
• Excessive H+ or decreased HCO3-
-
H2CO3 HCO 3 3-
HCO
H 2CO 3
== 7.4
7.4
1 : 10
20 94
High AG Metabolic
Acidosis
• Increase in Unmeasured Anions
Endogenous production – Lactate,
Pyruvate, Acetoacetate, β OH Butyrate
• Ingestion of Acids- Exogenous
Drugs, Poisoning
• Accumulation of endogenous acids
:Renal dysfunction
Enzymes
C6H12O6 2C3H6O3 + ATP (energy)
12/8/21
Lactic Acid
Causes
• Lactic Acidosis
• Keto Acidosis- DM, Alcohol,
Starvation
• Strenuous Exercise
• Toxins – Ethylene glycol,
Methanol, ethanol,
Salicylates, Propyl glycol,
Pyroglutamic acid
• Renal Failure- Acute and
Chronic
12/8/21
Normal / Low Anion gap
Metabolic acidosis
Loss of both Anions and cations
• GI loss – lower GI secretions -
Diarrhoea, GI fistula
• Renal tubular Acidosis – with
Hypo or Hyperkalemia
• Drugs - Diuretics
• Others – Acid loads, loss of
bicarbonate due to ketonuria,
Expansion acidosis,
Cation exchange resins.
12/8/21
Hyperchloremic Metabolic
Acidosis
12/8/21
Clinical Features :
RS CVS
Hyper Depressed CNS
ventilation contractility Headache
Kussmal’s Arrhythmias Lethargy
respiration decreased Stupor
Pulmonary vascular Coma
edema compliance
METABOLIC ACIDOSIS
H2CO3 : Carbonic Acid
HCO3- : Bicarbonate Ion
H2CO3 HCO3-
(Na+) HCO3-
(K+) HCO3-
1 : 20 (Mg++) HCO3-
(Ca++) HCO3-
-
HCO 3
H 2CO 3
= 7.4
1 : 10
- HCO3-
HCO 3
+
H 2CO 3 H+
CO2 + H2O
0.75 : 10
Acidic urine
Lactate
containing
solution
0.5 : 10
106
METABOLIC ALKALOSIS
• A reduction in H+ in the case of metabolic
alkalosis can be caused by a deficiency of non-
carbonic acids
• This is associated with an increase in HCO3-
107
METABOLIC ALKALOSIS
H2 CO HCO -
3 3
1 : 40
HCO3- increases because of loss of chloride ions or
excess ingestion of NaHCO3
pH = >7.45 108
METABOLIC ALKALOSIS
Causes:
1) Ingestion of Alkaline Substances
2) ECF with sec hyperaldosteronism
hyperreninism
Vomiting ( loss of HCl ), Aspiration
Diuretics
Hypercalcemia ( PTH)
Def of Mg+, K+
3) ECF ,HTN, K+ def, Mineralocorticoid
excess
Renin Renin
Liddle’s ,Gittlemann’s syndrome
109
Classification
• Chloride responsive
---- Loss of upper GI secretions
Responds to treatment with
Chloride solution
• Chloride resistant
-----Other causes which does not respond
to chloride treatment
12/8/21
METABOLIC ALKALOSIS
• Reaction of the body to alkalosis is to lower pH
by:
– Retain CO2 by decreasing breathing rate
– Kidneys increase the retention of H+
H+
H+
CO2 H+
CO2 H+
111
METABOLIC ALKALOSIS
HCO3- + H+
H+
H2CO3 HCO3 - +
CO2 + H2O HCO3-
1.25 : 30
BODY’S COMPENSATION Alkaline urine
Breathing suppressed to hold CO2
kidneys conserve H+ ions and eliminate HCO3- in alkaline
urine 112
Treatment
• Replacing water and electrolytes
(sodium and potassium)
• Chloride containing solution
• Treat the underlying cause
• Diuretics -Acetazolamide
• If very severe, dilute acid in the
form of Ammonium chloride or
0.1N HCL is given by IV
• Hemodialysis
113
Paradoxical Acidura
• Seen in Metabolic Alkalosis
• K+ deficient states,
• ACTH/Cortisone therapy /GI loss/Cushing’s
syndrome
12/8/21
References
• Harrison’s Principles of Internal Medicine 17th
Edition
• Clinical Physiology Of Acid Base &Electrolyte
Disorders- B D Rose
• T/B of Biochemistry –Pankaja Nayak
• T/B of Biochemistry –Vasudevan
• Google
12/8/21
Disorders of Acid Base Balance Contd……..
12/8/21
Respiratory Acidosis
The primary disturbance is an
[H2CO3] – Retention of CO2
Causes:
• Central: Drugs
Stroke, Infection, head injury
• Airway : Obstruction , Asthma
• Parenchyma: Emphysema,
Pneumoconiosis, Bronchitis,
ARDS,
• Neuromuscular : PM,
Kyphoscoliosis, MG, MD
• Miscellaneous : Obesity,
Hypoventilation
RESPIRATORY ACIDOSIS
• Caused by hypercapnia due to
Increased retention
Decreased elimination
H2CO3 pH
•
CO2
pH
CO2 CO2
CO2 CO2
CO CO2 CO2
2
12/8/21
RESPIRATORY ACIDOSIS
CO2 CO2
-
HCO 3 CO2
CO2
H 2CO 3
2 : 20
12/8/21
RESPIRATORY ACIDOSIS
H2CO3
-
HCO3-
CO
H 3 HCO3-
H 2CO 3
+
H+
2 : 30
acidic urine
BODY’S COMPENSATION
-kidneys conserve HCO3- ions to restore the
normal 40:2 ratio (20:1)
-kidneys eliminate H+ ion in acidic urine 122
Clinical features
• Depends on the severity of condition
• Increased PaCO2- Anxiety,dyspnoea,
psychosis, hallucinations , Coma
• Myotonic jerks, day time somnolence,
personality changes, tremors
• Increased ICP- Papilledema, Abnormal
reflexes, muscle weakness
12/8/21
Diagnosis
Arterial blood gases
History & Clinical examination (RS)
Pulmonary function tests – lung volumes,
Spirometry, Diffusion capacity of
CO2,SPO2
Non pulmonary causes: hematocrit,
neuromuscular function,
Treatment of respiratory acidosis
• If severe & life threatening: Treat underlying
cause & restore alveolar ventilation
simultaneosly
• Oxygen administration cautiously
• Sudden correction is hazardous
• Chronic – Improve the respiratory function
Respiratory Alkalosis
primary disturbance is decrease
of [H2CO3] in plasma
• CO2 H2CO3 pH
12/8/21
respiratory alkalosis
the Causes:
• Hysterical – Hyperventilation
syndrome
• Hypoxia- High altitude
• Injury to brain stem
• Raised ICP
• Drugs: Salicylate poisoning
• Iatrogenic: ventilator misoperation
RESPIRATORY ALKALOSIS
• Normal 20:1 ratio is increased
– pH of blood is above 7.4
H2H2 C3O
CO 3
HCO3-
HCO -
== 7.4
3
0.51 : 20
128
RESPIRATORY ALKALOSIS
• Kidneys compensate by:
– Retaining hydrogen ions
– Increasing bicarbonate excretion
HCO3-
HCO3-
H+
H+
HCO3- HCO3-
H+
H+ H+
HCO3-
HCO3- H+
HCO3-
H+
HCO3- H+
HCO 3
-
H+
HCO3- H
+
H+ 129
Clinical features
• Depends on the severity and duration
• Due to hypoperfusion
• Dizziness, Mental confusion, Seizures, Cardiac
arrythmias
• Hyperventilation, Parasthesia, numbness,
fatigue, chest wall tightness, dizziness, tetany
12/8/21
Diagnosis
History & Clinical examination (RS)
Arterial blood gases
Serum Electrolytes
12/8/21
Mixed Metabolic and respiratory
●
LA ●
Severe ●
Liver
●
Sepsis Pneumonia ●
COPD on disease
●
Salicylate ●
Pul Edema Diuretics and
poisoning ●
Drug Abuse diuretics
12/8/21
Mixed Metabolic Disorders
●
Diarrhoea with Lactic
Acidosis
●
Uraemia with Vomiting ●
Toluene toxicity
●
Treatment of DKA
12/8/21
triple acid-base disturbance
nary disease; ●
Alcoholic Keto
vomiting Acidosis
Acid Base Parameters
•
12/8/21
SEVEN STEPS TO ACID BASE ANALYSIS
(for highly effective clinicians!)
12/8/21
END
ACID - BASE BALANCE
139
12/8/21 Thank You